Pompey reestablished a number of cities and reduced the kingdom of Judaea; 10 cities of the interior formed a league, the Decapolis. The native client kingdoms of Commagene, Ituraea, Judaea, and Nabataea were henceforth subjected to Roman Syria. Parthian invasions were thrown back in 51-50 and 40-39 BC, and Mark Antony's extensive territorial gifts to Cleopatra (Ituraea, Damascus, Coele Syria, etc.) involved only temporary adjustments.

Under the early empire, Syria, which stretched northeast to the upper Euphrates and, until AD 73, included eastern Cilicia, became one of the most important provinces. Its governor, a consular legate, generally commanded four legions until AD 70. Administrative changes followed, as Rome gradually annexed the client kingdoms. Ituraea was incorporated (i.e., its territories were assigned to neighbouring cities) partly in 24 BC, partly c. AD 93. Judaea became a separate province in AD 6, governed by procurators (apart from the short-lived control by Agrippa I, AD 41-44), until the destruction of Jerusalem in 70. Then, the governor was a praetorian legate in command of a legion; next, under Hadrian, he was a consular with two legions, and the province was named Syria Palaestina. Commagene was annexed permanently by Vespasian in 72. The caravan city of Palmyra came under Roman control, possibly during Tiberius' reign. Finally, Nabataea was made the province of Arabia in 105, governed by a praetorian legate with one legion.

Syria itself was later divided by Septimius Severus into two provinces--Syria Coele in the north with two legions and Syria Phoenice with one. By the beginning of the 5th century it was subdivided into at least five provinces. The frontiers of Syria were guarded by a fortified limes system, which was thoroughly reorganized by Diocletian and his successors (particularly against cavalry attacks) and which endured until the Arab conquest.